Heroin and prescription opioid dependence among youth is a serious and growing public health problem that is associated with overdose death, HIV and hepatitis infection, criminal behavior and arrest. Despite the availability of buprenorphine, and, most recently, extended-release naltrexone (XR-NTX) for the treatment of opioid dependence, there are only limited data from two randomized trials of opioid detoxification with buprenorphine in youth and no data from trials using XR-NTX in this important patient population. This present proposal is a 6-month, two-group random assignment comparative effectiveness trial of XR- NTX v. Treatment as Usual (TAU) for 340 opioid-dependent youth ages 15-21. The study will be conducted at Mountain Manor Treatment Center, a community treatment program that has participated in a number of clinical trials of pharmacotherapy for youth with addictive disorders. Importantly, the study team has considerable experience using XR-NTX among adults and youth and has published the only report to date on the use of XR-NTX in youth. TAU will consist of the typical treatment approach provided to opioid-dependent youth in the US, namely buprenorphine for the treatment of opioid withdrawal followed by counseling with or without continued buprenorphine. The study's aims are: (1) to determine the relative effectiveness of XR-NTX compared to TAU for opioid- dependent youth in terms of the following 3- and 6-month outcomes: a) days in treatment; b) opioid use; c) other drug (cocaine and marijuana) and alcohol use; d) criminal behavior and arrests; and e) relapse to DSM- IV defined opioid dependence; (2) to examine the impact of XR-NTX on HIV drug- and sex-risk behaviors at 3- and 6-month follow-up and HIV infection status at 6-months; and (3) to evaluate the cost, cost-effectiveness, and cost-benefit of XR-NTX v. TAU among opioid-dependent youth. This application is of high public health significance given the growth of opioid use and dependence among youth and their associated public health and safety problems. It is highly innovative as it will provide novel data regarding the effectiveness f XR-NTX in this patient population and it will provide novel cost-benefit data. The proposed project's findings have the potential to impact patients, public health, and public safety by reducing opiate use and its collateral problems among this vulnerable population.